tbuckley/cabot-search huggingface dataset:
Bi-allelic hydroxymethylbilane synthase inactivation defines a homogenous clinico-molecular subtype of hepatocellular carcinoma
Authors: Laura Molina, Junjie Zhu, Eric Trépo, Quentin Bayard, Giuliana Amaddeo, Jean-Frédéric Blanc, Julien Calderaro, Xiaochao Ma, Jessica Zucman-Rossi, Eric Letouzé, Brigitte Le Bail, Laurence Chiche, Paulette Bioulac-Sage, Charles Balabaud, Laurent Possenti, Marie Decraecker, Valérie Paradis, Alexis Laurent
Journal: Journal of Hepatology (2022)
Using infrared spectroscopy to analyze breath of patients diagnosed with breast cancer.
Authors: Farah Naz, Amy Grace Groom, MD Mohiuddin, Arpita Sengupta, Trisha Daigle-Maloney, Margot J. Burnell, James Charles Roger Michael, Stephen Graham, Gisia Beydaghyan, Erik Scheme, Angkoon Phinyomark, Robyn Larracy
Journal: Journal of Clinical Oncology (2022)

e13579 Background: Population-level screening programs aimed at early detection and treatment of breast cancer saves lives. Analyzing breath using infrared spectroscopy offers a highly sensitive, non-invasive, and cost-effective mechanism for identifying exhaled volatile organic chemicals, and it is hypothesized that it may identify differences in the “breathprint” of women with breast cancer relative to those without a breast cancer diagnosis. Methods: Alveolar breath samples (10 L) were collected using a Breathe BioMedical alveolar breath sampler onto Tenax TA sorbent tubes. Corresponding room air samples (10 L) were collected in the same manner. Absorption spectra of the samples at a desorb temperature of 75 °C were measured by infrared cavity ring-down spectroscopy (IR-CRDS), a highly sensitive method of measuring absorption coefficients due to trace volatile organic compounds (VOCs) present in exhaled breath. After subtracting room air absorption and ordering each measured spectrum by increasing wavelength, missing values were imputed using spline interpolation. The absorption spectra were then normalized using one of four techniques: min-max, vector, peak or standard normal variate normalization. The first derivatives of the normalized absorption coefficients (187 values in total) were then used as features for discriminating samples from subjects with breast cancer and controls. The most useful features were selected based on minimum redundancy and maximum relevance (mRMR) and were used to train a linear support vector machine (SVM) classifier. Performance of classification models was estimated based on two data splitting configurations, non-nested leave-one-out cross-validation (LOOCV) and nested LOOCV. These approaches provide upper and lower bounds of expected model performance. Classification performance was used for tuning the number of features included in each model. Results: The analysis of this study is based on the spectra obtained from 70 participants (38 breast cancer and 32 controls), collected at the Saint John Regional Hospital in New Brunswick, Canada. Table below shows the non-nested and nested performance characteristics of classifiers with the best performing normalization technique. The number of features given for the nested model is not an integer as it indicates an average across the cross-validation folds. Conclusions: These results suggest that the classification of alveolar breath using IR-CRDS is a promising technique for the detection of breast cancer. Performance of classification models. AUC is the area under the receiver operator characteristics curve.[Table: see text]
CD69 expression on Treg cells prevents chronic heart damage after myocardial infarction
Authors: R Blanco Dominguez, L Martin-Aguado, H De La Fuente, C Rodriguez, R Jimenez-Alejandre, I Rodriguez-Arabaolaza, MM Garcia-Guimaraes, A Vera, J Cuesta, A Cecconi, F Alfonso, F Sanchez-Madrid, J Martinez-Gonzalez, P Martin
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministerio de Ciencia e Innovación (MCIN), through the Carlos III Institute of Health (ISCIII)-Fondo de Investigación Sanitaria (PI19/00545) Background Increasing evidences advocate for an important function of T cells in controlling immune homeostasis and pathogenesis after myocardial infarction (MI), although the molecular mechanisms remain elusive. Result and Methods In this study, a broad analysis of immune markers in 283 patients show a significant CD69 overexpression on Treg cells after MI. Our results in mice demonstrate that CD69 expression on Treg cells increases survival after left-anterior-descending coronary artery (LAD)-ligation. Cd69-/- mice develop strong IL17A+ gdT cell responses after ischemia that increase myocardial inflammation and, consequently, worsen cardiac function. CD69+ Treg cells induce apoptosis and decrease IL-17A production in gdT cells by a CD39-dependent mechanism. Adoptive transfer of CD69+ Treg cells to Cd69-/- mice after LAD-ligation reduces IL17A+ gdT cell recruitment increasing survival. Consistently, clinical data from two independent cohorts of patients indicate that increased CD69 expression in peripheral blood cells after acute MI is associated with a lower risk of re-hospitalization for chronic heart failure (CHF) after 2.5 years of follow-up. This result remained significant after adjustment for age, sex and traditional cardiac damage biomarkers (OR 0.929, 95% CI, 0.838-0.980; p&amp;lt;0.0409). Conclusion Our data highlight CD69 expression on T cells as a therapeutic and prognostic target to prevent CHF after MI.
Proteomics to assess myocardial remodelling in human heart failure and explore the effect of medications and comorbidities
Authors: J Barallobre-Barreiro, T Radovits, M Fava, L Daroczi, M Hasman, L Schmidt, F Baig, K Theofilatos, MG Crespo-Leiro, N Domenech, B Merkely, M Mayr
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background Myocardial remodelling is a hallmark of heart failure (HF). Our previous proteomics analyses demonstrated a profound effect of beta blockers on cardiac extracellular matrix composition in ischaemic HF patients (1). No comprehensive proteomics characterizations has been performed in non-ischaemic HF patients. Methods Mass spectrometry was used to analyze intracellular and extracellular protein extracts from left ventricular samples obtained from patients with ischemic (n=65) and non-ischaemic (n=114) HF after heart transplantation, as well as non-failing controls (n=19). All HF patients had ventricular dilatation and reduced ejection fraction (EF%). Results The proteomics comparison across 198 cardiac samples with two tissue extracts revealed hallmarks of HF in both groups of patients compared to controls, including elevated levels of atrial natriuretric peptides and the fibroblast marker vimentin, as well as decreases in creatine kinase M/B, troponin C, and myosin light chain 2 (Figure 1). In comparison to ischaemic HF patients, non-ischaemic HF patients showed elevated levels of proteins involved in proteasome activation, consistent with the notion of increased protein degradation in cardiomyocytes even at the end stage of the disease (2). Despite similar clinical characteristics, myocardial remodelling in response to HF medications and the presence of comorbidities was different between the two HF groups. In ischaemic HF patients the use of β-blockers resulted in reduced proteoglycan deposition. In non-ischaemic patients, few protein changes were associated with medication. Instead, comorbidities such as atrial fibrillation and hypertension were critical determinants of myocardial protein remodelling in these HF patients (Figure 2). Notably, hypertensive HF patients showed a marked reduction in angiotensin converting enzyme 2 (ACE2) compared to normotensive patients, and this was accompanied by a reduction in Cysteine And Glycine Rich Protein 3 (CSRP3), a key player in the organization of cytosolic structures in cardiomyocytes, and the nuclear lamina proteins lamin A/C and B. The inflammation-related galectin 3-binding protein was reduced in hypertensive patients as were the extracellular proteases matrix metalloprotease 2, cathepsin G and chymase 1. Conclusion Our study constitutes the largest proteomics analysis of HF to date. We observed distinct protein remodelling processes in ischaemic and non-ischaemic HF patients and discerned the myocardial effects of medications and comorbidities such as hypertension.
Impact of imbalanced gender participation in online myeloproliferative neoplasm symptom surveys.
Authors: Blake Langlais, Gina L. Mazza, Robyn Marie Scherber, Holly Geyer, Krisstina L. Gowin, Jeanne Palmer, Heidi E. Kosiorek, Carolyn Mead-Harvey, Richard Butterfield, Ruben A. Mesa, Amylou C. Dueck
Journal: Journal of Clinical Oncology (2022)

e19078 Background: Patients with myeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), experience chronic disease-related symptoms. Surveying these patients while incorporating the MPN-Symptom Assessment Form (SAF) gains valuable insight. Independent surveys evaluating symptoms among MPN patients have seen disproportionate participation among females compared to males (upwards of 4:1). Though the general MPN patient population is roughly gender balanced, epidemiological studies show the occurrence of MPN types differ between men and women (MPN [%male]: PV [65%], ET [33%], MF [50%]. Mehta, et al. Leuk &amp; Lymph 2014). In-clinic evaluations and international MPN surveys of disease-related symptoms suggest women report higher symptom burden on average compared to men, despite MPN type [Emanuel, et al. JCO 2012. Geyer, et al. Haematol 2017]. Further, a recent study across cancer trials showed women had a 34% increased risk of reporting severe symptoms [Unger, et al. JCO 2022]. This study aimed to evaluate gender imbalance in survey participation among MPN patient surveys and investigate its potential to overestimate symptom burden if gender is ignored. Methods: Five anonymous web-based surveys were used to assess the impact of disproportionate gender participation. The MPN-10 assessing the 10 most clinically meaningful SAF items was present in these surveys and generated the Total Symptom Score (TSS). Survey responses with no self-reported gender or ≥5 missing MPN-10 symptoms were excluded. Raking weights based on expected MPN population were applied at the survey- and MPN type-level. Relative bias of mean TSS was calculated to evaluate over- and underestimation due to this participation imbalance. Relative bias &lt;5% is commonly acceptable. Results: There were 4962 survey participants total and 74% were female (Table). Epidemiologically expected gender frequency by MPN type was not seen (MPN [%male]: PV [31%], ET [15%], MF [37%]). The gender participation imbalance accounted for a 3.1% overestimation of overall TSS. This also resulted in a 6.8% underestimation of the mean difference in TSS between genders, across MPNs. Conclusions: Overall bias due to gender participation imbalance was relatively low. However, analyses considering gender differences were more impacted. Anonymous surveys should seek to reduce participation bias during the survey design phase. More research is needed to evaluate gender and other participation biases in surveys across cancer domains.[Table: see text]
Genomic Signatures of Divergent Ecological Strategies in a Recent Radiation of Neotropical Wild Cats
Authors: Jorge L. Ramirez, Jonas Lescroart, Henrique V. Figueiró, Juan Pablo Torres-Florez, Priscilla M. S. Villela, Luiz L. Coutinho, Patricia D. Freitas, Warren E. Johnson, Agostinho Antunes, Pedro M. Galetti, Eduardo Eizirik
Journal: Molecular Biology and Evolution (2022)

Abstract Ecological differentiation among diverging species is an important component of the evolutionary process and can be investigated in rapid and recent radiations. Here, we use whole genome sequences of five species from the genus Leopardus, a recently diversified Neotropical lineage with species bearing distinctive morphological, ecological, and behavioral features, to investigate genome-wide diversity, comparative demographic history and signatures of positive selection. Our results show that divergent ecological strategies are reflected in genomic features, for example a generalist species shows historically larger effective population size and higher heterozygosity than habitat specialists. The demographic history of these cats seems to have been jointly driven by climate fluctuations and habitat specialization, with different ecological adaptations leading to distinct trajectories. Finally, a gene involved in vertebrate retinal neurogenesis (POU4F2) was found to be under positive selection in the margay, a cat with notoriously large eyes that are likely associated with its nocturnal and arboreal specializations.
The mechanosensitive ion channel PIEZO1 is expressed in tendons and regulates physical performance
Authors: Ryo Nakamichi, Shang Ma, Takayuki Nonoyama, Tomoki Chiba, Ryota Kurimoto, Hiroki Ohzono, Merissa Olmer, Chisa Shukunami, Noriyuki Fuku, Guan Wang, Errol Morrison, Yannis P. Pitsiladis, Toshifumi Ozaki, Darryl D’Lima, Martin Lotz, Ardem Patapoutian, Hiroshi Asahara
Journal: Science Translational Medicine (2022)

How mechanical stress affects physical performance via tendons is not fully understood. Piezo1 is a mechanosensitive ion channel, and E756del PIEZO1 was recently found as a gain-of-function variant that is common in individuals of African descent. We generated tendon-specific knock-in mice using R2482H Piezo1, a mouse gain-of-function variant, and found that they had higher jumping abilities and faster running speeds than wild-type or muscle-specific knock-in mice. These phenotypes were associated with enhanced tendon anabolism via an increase in tendon-specific transcription factors, Mohawk and Scleraxis, but there was no evidence of changes in muscle. Biomechanical analysis showed that the tendons of R2482H Piezo1 mice were more compliant and stored more elastic energy, consistent with the enhancement of jumping ability. These phenotypes were replicated in mice with tendon-specific R2482H Piezo1 replacement after tendon maturation, indicating that PIEZO1 could be a target for promoting physical performance by enhancing function in mature tendon. The frequency of E756del PIEZO1 was higher in sprinters than in population-matched nonathletic controls in a small Jamaican cohort, suggesting a similar function in humans. Together, this human and mouse genetic and physiological evidence revealed a critical function of tendons in physical performance, which is tightly and robustly regulated by PIEZO1 in tenocytes.
Reply to Jinze Li, Yin Huang, Dehong Cao, and Qiang Wei’s Letter to the Editor re: Øyvind Ulvik, Mathias Sørstrand Æsøy, Patrick Juliebø-Jones, Peder Gjengstø, Christian Beisland. Thulium Fibre Laser Versus Holmium:YAG for Ureteroscopic Lithotripsy: Outcomes from a Prospective Randomised Clinical Trial. Eur Urol. 2022;82:73–79
Authors: Øyvind Ulvik, Mathias Sørstrand Æsøy, Patrick Juliebø-Jones, Peder Gjengstø, Christian Beisland
Journal: European Urology (2022)
OTHR-03. Oxaliplatin as a hearing-sparing alternative to carboplatin in tandem autologous stem cell transplants in pediatric CNS malignancy
Authors: Soohee Cho, Kristen Miller, Jacqueline Rowley, Ashley Sabus, Shelby Winzent-Oonk, Stacy Bray, Jane Koo, Jean Mulcahy Levy
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Intensive chemotherapy with tandem autologous stem cell transplants (autoSCT) is shown to improve survival for children with CNS malignancy. Platinum-based chemotherapeutic agents in these regimens, mainly cisplatin and carboplatin, have resulted in significant sensorineural hearing loss. Oxaliplatin, a newer platinum-based agent, is considered less ototoxic. Empiric substitution of oxaliplatin for carboplatin in preparative regimens for autoSCT have been tried. However, the survival and ototoxicity outcomes have not been studied. OBJECTIVE: To compare the overall survival and ototoxicity of oxaliplatin versus carboplatin preparatory chemotherapy regimens in children who received tandem autoSCT for treatment of CNS malignancy. METHODS: We performed a retrospective chart review of all pediatric patients with primary CNS tumors who received tandem autoSCT from 2011 to 2018 at Children’s Hospital Colorado. Demographics, clinical outcomes, and medication administration records were extracted from electronic medical records. Hearing evaluations, performed at pre-transplant, after each transplant episode, and at follow-up visits, were reviewed and graded by an audiologist. Comparisons were performed using Fisher’s exact tests and log rank test statistics. RESULTS: 32 pediatric patients with CNS tumors met inclusion criteria. Seven patients received oxaliplatin in place of carboplatin in one or more preparatory regimens. There was no statistically significant difference in overall survival between the two groups (p=0.99). A total of 85 follow-up audiograms were available for assessment, including long-term follow up. Of the 13 audiograms that showed hearing loss, one (8%) had prior oxaliplatin exposure, compared to 18/72 (25%) audiograms without hearing loss had prior oxaliplatin exposure (p=0.28). CONCLUSIONS: Oxaliplatin is effective and well-tolerated when used in lieu of carboplatin in preparatory regimen for autoSCT for pediatric CNS malignancy. This study is limited by its small size. A larger, multi-center study is warranted to confirm oxaliplatin’s safety and effect on survival and ototoxicity in pediatric autoHSCT.
Prevalence of antecipatory nausea and vomiting in cancer patients exposed to highly emetogenic chemotherapy.
Authors: Rafaela de Brito Alves, Camilla Vieira de Reboucas, Louize Caroline Marques Oliveira, Alayne Magalhaes Trindade Domingues Yamada, Felipe Melo Cruz
Journal: Journal of Clinical Oncology (2022)

e24112 Background: Anticipatory nausea (AN) and vomiting are unpleasant symptoms observed in anticipation of chemotherapy regimens. It is best described as a learned response through classical conditioning when one or more distinctive features of the chemotherapy clinic (conditioned stimuli) associated with the administration of emetogenic chemotherapy (unconditioned stimuli) trigger the emetogenic reflex. Little is known about AN's occurrence after the advent of the new neurokinin-1 antagonist. This prospective study evaluated AN's prevalence in ambulatory breast cancer patients receiving high effective antiemetic prophylaxis and evaluated potential predictors of AN. Methods: This prospective observational study was performed at a single Brazilian Institution. Key inclusion criteria were patients aged 18 years or older with breast cancer scheduled to receive anthracycline chemotherapy with an appropriate antiemetic regimen, including a neurokinin-1 receptor antagonist, a serotonin-3 receptor antagonist, and a corticosteroid. Eligible patients used a diary to record nausea, vomiting, and use of rescue medication in the first 2-cycle of treatment through 120 after infusion. AN was assessed before chemotherapy on day 1 of cycle two. We excluded patients with nausea and vomiting presented 24h before cycle one and patients who did not receive standard antiemetic prophylaxis. Results: Between August 04, 2020, and August 12, 2021, 60 patients were screened, and 52 patients were enrolled. The mean age was 50,8 (28 – 69), the majority had stage III (53,8%) and received chemotherapy with curative intent (94%). During cycle 1, the frequency of overall nausea and vomiting was 67.31%, and severe nausea and vomiting (defined as grade &gt; 4 at a 10-point visual scale or use of rescue medication) was 55.77%. Ten patients had AN (19.23%). The occurrence of nausea and vomiting during cycle one was the only statistically significant predictor of AN (OR = 16, 95% CI 2.4, 670.9, p-value = 0.0003). Conclusions: The prevalence of AN is still high in the era of neurokinin-1 antagonists, and failure of antiemetic control on cycle one remains the main risk factor. All efforts should be made to control chemotherapy-induced nausea or nausea and vomiting on cycle one to avoid AN. Clinical trial information: NCT04785495.
Trends in cancer diagnosis during the SARS-CoV-2 pandemic.
Authors: Tamara Lynne Bautista Aqui, Andrew Hwang, Napatkamon Ayutyanont, Erica Junqueira
Journal: Journal of Clinical Oncology (2022)

e18584 Background: In a national survey 40.9% of 4,975 adults reported delaying or avoiding care due to concerns over COVID-19. Avoidance of medical care with lockdown and a decrease in access to services carries the possibility of increased morbidity and mortality from metastatic disease due to delays in diagnosis. We examine the trends in cancer diagnosis in admitted adult patients, comparing the incidences of diagnoses before lockdowns, after lockdowns, and as restrictions were lifted. Increase in diagnoses linked with metastatic disease in the late pandemic compared to early when lockdowns occurred would show delays in care due to decreased access from the pandemic, and likely increase in morbidity and mortality. Methods: Data was retrospectively analyzed patients admitted to HCA hospitals March 2020 to December 2021, separated to three periods: pre (Mar 2019-Feb 2020), early (Mar 2020-November 2020) and late pandemic (Dec 2020-December 2021). 66,022 patients with ICD-10 codes matching malignancies of lung, small intestine, colorectal, pancreas, breast, or cervix were included and patients that additionally had ICD-10 codes for metastatic disease were identified. Patients with unlinked metastatic disease codes were removed. Population demographics including sex, race, ethnicity, insurance were also included. Results: There was a decrease in lung cancer diagnoses in the pre-pandemic period from 6,546 to early at 3,248, and an increase in the late period to 4,763. Diagnoses of metastatic disease with lung cancer decreased from 4,143 in pre-pandemic to 3,357 in late pandemic. Colorectal cancer (CRC) patients without metastatic disease pre-pandemic numbered at 5,836; 3,717 early pandemic; and 5,672, late pandemic. Diagnoses with metastatic disease decreased from 2,980 to 2,511 in the late period. Pancreatic cancer diagnoses decreased from 1,623 pre-pandemic to 1,508 late pandemic. Associated metastatic disease decreased from 1,181 pre-pandemic to 1,061 late pandemic. Breast cancer diagnoses decreased from 2,241 pre-pandemic to 1,915 late pandemic, and diagnoses with metastatic disease decreased from 2,334 to 1,711. Cervical cancer diagnoses increased from 385 pre-pandemic to 444 late pandemic and diagnoses with metastatic disease decreased from 252 to 187 in the late pandemic. Conclusions: Delays in access to care due to the pandemic are reflected in decreases of diagnoses seen. There was a decrease in lung, colorectal, pancreatic, breast, and cervical cancer diagnoses in the early pandemic period likely due to lockdown and diversion of medical effort. In the late pandemic period, diagnoses of these cancers rose, reflecting loosened restrictions. Our study is not able to determine the impact of delayed diagnosis, but likely results in increased morbidity and mortality. These effects could be mitigated in the future with uninterrupted access to telehealth and cancer screening.